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. 2012 Dec;42(12):1734-44.
doi: 10.1111/cea.12005.

Nasal cytokine responses to natural colds in asthmatic children

T C Lewis  1 , T A Henderson, A R Carpenter, I A Ramirez, C L McHenry, A M Goldsmith, X Ren, G B Mentz, B Mukherjee, T G Robins, T A Joiner, L S Mohammad, E R Nguyen, M A Burns, D T Burke, M B Hershenson
Affiliations

Nasal cytokine responses to natural colds in asthmatic children

T C Lewis et al. Clin Exp Allergy. 2012 Dec.

Abstract

Background: The mechanisms by which viruses induce asthma exacerbations are not well understood.

Objective: We characterized fluctuations in nasal aspirate cytokines during naturally occurring respiratory viral infections in children with asthma.

Methods: Sixteen children underwent home collections of nasal aspirates when they were without cold symptoms and again during self-reported respiratory illnesses. The presence of viral infection was ascertained by multiplex PCR. Cytokines were measured using multiplex immune assay. mRNA expression for selected markers of viral infection was measured using RT-PCR. A cumulative respiratory symptom score was calculated for each day of measurement. Generalized estimated equations were used to evaluate associations between viral infection and marker elevation, and between marker elevation and symptom score.

Results: The 16 patients completed a total of 37 weeks of assessment (15 'well' weeks; 22 self-assessed 'sick' weeks). Viral infections were detected in 3 of the 'well' weeks and 17 of the 'sick' weeks (10 rhinovirus, three coronavirus, two influenza A, two influenza B, two respiratory syncytial virus, one parainfluenza). Compared to virus-negative well weeks, nasal aspirate IFN-γ, CXCL8/IL-8, CXCL10/IP-10, CCL5/RANTES, CCL11/eotaxin-1, CCL2/MCP-1, CCL4/MIP-1β, CCL7/MCP-3, and CCL20/MIP3α protein levels increased during virus-positive sick weeks. Only a subset of cytokines (IFN-γ, CXCL8, CCL2, CCL4, CCL5, and CCL20) correlated with self-reported respiratory tract symptoms. While many aspirates were dilute and showed no mRNA signal, viral infection significantly increased the number of samples that were positive for IFN-λ1, IFN-λ2/3, TLR3, RIG-I, and IRF7 mRNA.

Conclusions and clinical relevance: We conclude that in children with asthma, naturally occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs, and IFN-responsive genes.

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Figures

Figure 1
Figure 1
(a) Time course of symptom scores. Skeletal box and whiskers plot shows interquartile range (box), minimum and maximum observations (whiskers), and mean (closed circle). Average symptom scores during the weeks of baseline assessment, when virus was not detected, represent the healthy state. Day 1 of the viral illness was defined as the day families reported a respiratory symptoms score ≥ 2. s1–3 represents average symptoms on days 1–3 of the illness, and so on. Data for sick, virus‐positive weeks are shown. (b) Modelled effect of confirmed virus on cytokine concentration. Cytokine concentration was mathematically transformed ln (y + 1) prior to modelling and estimates are shown on this scale. Models were adjusted for age, gender, race, and nasal steroid use.
Figure 2
Figure 2
Time course of nasal lavage cytokines comparing healthy week to early (s1–2), mid (s3–6), and late (s7–12) phases of self‐reported sick periods that had a confirmed viral infection.
Figure 3
Figure 3
Time course of exhaled nitric oxide values. FeNO was measured using the NIOX MINO (Aerocrine, New Providence, NJ, USA).
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